title: Targeted disruption of one of the importin α family members leads to female functional incompetence in delivery.
abstract: Importin α mediates the nuclear import of proteins through nuclear pore complexes in eukaryotic cells, and is common to all eukaryotes. Previous reports identified at least six importin α family genes in mice. Although these isoforms show differential binding to various import cargoes in vitro, the in vivo physiological roles of these mammalian importin α isoforms remain unknown. Here, we generated and examined importin α5 knockout (impα5(-/-)) mice. These mice developed normally, and showed no gross histological abnormalities in most major organs. However, the ovary and uterus of impα5(-/-) female mice exhibited hypoplasia. Furthermore, we found that impα5(-/-) female mice had a 50% decrease in serum progesterone levels and a 57% decrease in progesterone receptor mRNA levels in the ovary. Additionally, impα5(-/-) uteruses that were treated with exogenous gonadotropins displayed hypertrophy, similarly to progesterone receptor-deficient mice. Although these mutant female mice could become pregnant, the total number of pups was significantly decreased, and some of the pups were dead at birth. These results suggest that importin α5 has essential roles in the mammalian female reproductive organs.
authors.affiliation: Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Moriyama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nagai
authors.forename: Masahiro
authors.initials: M
authors.lastname: Oka
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Okabe
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoneda
mesh_terms: D000818:Animals; D036861:Delivery, Obstetric; D005260:Female; D005836:Genitalia, Female / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D011270:Pregnancy, Animal; D011374:Progesterone / Q000097:blood; D011960:Receptors, Estrogen / Q000235:genetics; D028901:alpha Karyopherins / Q000235:genetics / Q000502:physiology*
chemical_list: C527077:KPNA1 protein, mouse; D011960:Receptors, Estrogen; D028901:alpha Karyopherins; D011374:Progesterone